Scientists looked at how two natural copper‑binding peptides, GHK and DAHK, hold onto copper atoms and how easily they give them up. They found that GHK‑Cu sticks together in a simple, single‑unit form in the body and can be reduced to copper‑I at relatively low voltages, which makes the copper detach. DAHK‑Cu stays more tightly bound and doesn’t release copper as easily. The work mainly maps out the chemistry rather than testing health effects.

The Gly-His-Lys (GHK) peptide and the Asp-Ala-His-Lys (DAHK) sequences are naturally occurring high-affinity copper(II) chelators found in the blood plasma and are hence of biological interest. A structural study of the copper complexes of these peptides was conducted in the solid state and in solution by determining their X-ray structures, and by using a large range of spectroscopies, including EPR and HYSCORE (hyperfine sub-level correlation), X-ray absorption and (1)H and (13)C NMR spectroscopy. The results indicate that the structures of [Cu(II)(DAHK)] in the solid state and in solution are similar and confirm the equatorial coordination sphere of NH(2), two amidyl N and one imidazole N. Additionally, a water molecule is bound apically to Cu(II) as revealed by the X-ray structure. As reported previously in the literature, [Cu(II)(GHK)], which exhibits a dimeric structure in the solid state, forms a monomeric complex in solution with three nitrogen ligands: NH(2), amidyl and imidazole. The fourth equatorial site is occupied by a labile oxygen atom from a carboxylate ligand in the solid state. We probe that fourth position and study ternary complexes of [Cu(II)(GHK)] with glycine or histidine. The Cu(II) exchange reaction between different DAHK peptides is very slow, in contrast to [Cu(II)(GHK)], in which the fast exchange was attributed to the presence of a [Cu(II)(GHK)(2)] complex. The redox properties of [Cu(II)(GHK)] and [Cu(II)(DAHK)] were investigated by cyclic voltammetry and by measuring the ascorbate oxidation in the presence of molecular oxygen. The measurements indicate that both Cu(II) complexes are inert under moderate redox potentials. In contrast to [Cu(II)(DAHK)], [Cu(II)(GHK)] could be reduced to Cu(I) around -0.62 V (versus AgCl/Ag) with subsequent release of the Cu ion. These complete analyses of structure and redox activity of those complexes gave new insights with biological impact and can serve as models for other more complicated Cu(II)-peptide interactions.